The uptake of glutamate in rat glioma C-6 cells and cultured astrocytes derived from newborn rat cerebral hemispheres was found to be mediated by glutamate/aspartate system (System X^-_) and cystine/glutamate exchange system (System x^-_). In C-6 cells the glutamate uptake via System X^-_ and x^-_ approximately accounted for 35% and 55% of the total uptake, respectively, at 0.05 mM glutamate. In cultured astrocytes the glutamate uptake via System X^-_ was very potent, whereas the uptake vis System x^-_ was relatively weak and its contribution to the total uptake of glutamate seemed almost negligible. However, in both C-6 cells and astrocytes System x^-_ was necessary for the uptake of cystine. Cystine in the culture medium was an essential precursor of glutathione and the inhibition of the cystine uptake via System x^-_ led to a severe deficiency in glutathione. Brain cells prepared from fetal rat (16 days gestation) showed a System x^-_ activity. These cells differentiated to neuron-like cells and astrocyte-like cells when cultured. Astrocyte-like cells showed a high activity of System x^-_ whereas neuron-like cells showed a very low activity. A glutathione level of neuron-like cells was maintained when they were co-cultured with astrocyte-like cells, but the level went down when they were separated from astrocyte-like cells. It was suggested that astrocytes took up cystine via System x^-_ and reduced it to cysteine, which was released from the cells and utilized by neurons to maintain their glutathione level.一方、胎生16日のラット大脳から細胞を取りだし、培養系で分化させχ^ー_c系の活性を調べた。取りだしたばかりの未分化大脳細胞は一定のシスチン取りこみ活性(χ^ー_c系による)を示したが、培養系で神経細胞とグリア細胞に分化するにつれ、この輸送活性は細胞全体としては数倍に上昇することが認められた。分化した神経細胞とグリア細胞を分離して調べると、グリア細胞では活性が高く、神経細胞では逆に活性が低かった。神経細胞はグリア細胞と共存していればグルタチオンを維持できるが、グリア細胞から離されると、シスチン取りこみ活性が低いため、グルタチオンを維持できないことが分った。すなわち、グリア細胞はχ^ー_c系によりシスチンを取りこみ、システインに還元してグルタチオン合成などに利用するが、一部のシステインを細胞外に放出し、それを神経細胞が中性アミノ酸輸送系で取りこみ、自らのグルタチオン合成に利用していると推定された。